Effects of early postnatal hyperglycaemia on renal cortex maturity, endothelial nitric oxide synthase expression and nephron deficit in mice.

The influence of hyperglycaemia on nephrogenesis on Swiss mice pups treated with streptozotocin (STZ) (40 mg/kg, i.p.) was studied after birth, at 7 and 21 days. Kidneys were prepared for light microscopy, immunohistochemistry and stereology. In 7-day-old pups, both immature and mature glomeruli were evaluated separately. Proliferating cell nuclear antigen (PCNA) and endothelial nitric oxide synthase (eNOS) immunostaining were performed and quantified. At age 7 days, the immature-to-mature glomeruli ratio (IMGR) was significantly higher in the STZ group than in the control group. There was no difference in the number of glomeruli between the STZ and control groups; however, the number of glomeruli increased by more than 20% in the control group until 21 days of age, but not in the STZ group. STZ pups showed numerous PCNA-positive nuclei mainly in tubular cells, but not control pups. At 21 days, eNOS expression in the outer layer of glomerular endothelial nuclei was strong in control pups, but weaker in STZ pups. Treatment with STZ during the early neonatal period disturbs the normal nephrogenesis occurring at this stage of the rodent's life and causes retardation in renal cortical maturity, as indicated by the increase in both PCNA expression and IMGR, and reduction in eNOS expression.